Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/02 23:06:35」(JST)
wiki en
| Systematic (IUPAC) name | |
|---|---|
|
(3S,4R)-3-[(2H-1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine
|
|
| Clinical data | |
| Trade names | Paxil, Pexeva, Seroxat, Brisdelle, Rexetin |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a698032 |
| Licence data | US FDA:link |
| Pregnancy category |
|
| Legal status |
|
| Routes of administration |
Oral |
| Pharmacokinetic data | |
| Bioavailability | Extensively absorbed from the GI tract, but extensive first-pass metabolism in the liver[1][2][3][4] |
| Protein binding | 93–95%[1][2][3] |
| Metabolism | Extensive, hepatic (mostly CYP2D6-mediated)[1][2][3] |
| Biological half-life | 21 hours[1][2][3] |
| Excretion | Renal (64%; 2% unchanged and 62% as metabolites), Faecal (36%; <1% unchanged)[1][2][3] |
| Identifiers | |
| CAS Number | 61869-08-7 Y |
| ATC code | N06AB05 |
| PubChem | CID: 43815 |
| IUPHAR/BPS | 4790 |
| DrugBank | DB00715 Y |
| ChemSpider | 39888 Y |
| UNII | 41VRH5220H Y |
| KEGG | D02362 Y |
| ChEBI | CHEBI:7936 N |
| ChEMBL | CHEMBL490 Y |
| Chemical data | |
| Formula | C19H20FNO3 |
| Molecular mass | 329.3 g/mol |
|
SMILES
|
|
|
InChI
|
|
| N (what is this?) (verify) | |
Paroxetine (also known by the trade names Paxil and Seroxat, among others) is an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) type. Paroxetine is used to treat major depression, obsessive-compulsive disorder, panic disorder, social anxiety, posttraumatic stress disorder, generalized anxiety disorder and vasomotor symptoms (e.g. hot flashes and night sweats) associated with menopause[5][6] in adult outpatients.
Differences between newer antidepressants are usually fairly subtle and mostly confined to side effects. Paroxetine shares the common side effects and contraindications of other SSRIs.[7] Discontinuing paroxetine is associated with a high (7%) risk of withdrawal syndrome.[8][9] It may be associated with a slightly increased risk of birth defects.[10][11][12] Several studies have associated paroxetine with suicidal thinking and behavior in teenagers.[13]
Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, known since 2000 as GlaxoSmithKline. Generic formulations have been available since 2003 when the patent expired.[14] The United States Department of Justice fined GlaxoSmithKline $3 billion in 2012, including a sum for withholding data on paroxetine, unlawfully promoting it for the under-18s, and preparing an article, following one of its clinical trials, study 329, that misleadingly reported the drug was effective in treating adolescent depression.[n 1]
Contents
- 1 Medical uses
- 1.1 Depression
- 1.2 Menopausal hot flashes
- 2 Adverse effects
- 2.1 Suicide
- 2.2 Pregnancy
- 2.3 Discontinuation syndrome
- 3 Overdose
- 4 Interactions
- 5 Pharmacology
- 6 Society and culture
- 6.1 Withdrawal symptoms
- 6.2 Off-label marketing for children
- 6.3 Sales
- 6.4 Trade names
- 7 Research
- 8 Notes
- 9 References
- 10 External links
Medical uses
Paroxetine is primarily used to treat major depression, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder, generalized anxiety disorder (GAD),[18] social phobia/social anxiety disorder,[19] premenstrual dysphoric disorder (PMDD)[20] and menopausal hot flashes.
Paroxetine was the first antidepressant formally approved in the United States for the treatment of panic attacks.[21]
Depression
A variety of meta analyses have been conducted to evaluate the efficacy of paroxetine in depression. They have variously concluded that paroxetine is superior[22][23][24] or equivalent[25] to placebo and that it is equivalent[26][27] or inferior[28] to other antidepressants.
Menopausal hot flashes
On June 28, 2013 U.S. FDA approved low dose paroxetine for the treatment of moderate-to-severe vasomotor symptoms (e.g. hot flashes and night sweats) associated with menopause.[29] Randomized controlled trials have shown modest relief in such cases. At the low dose used for menopausal hot flashes side effects are similar to placebo and dose tapering is not required for discontinuation.[30]
Adverse effects
See also: List of adverse effects of paroxetine
Paroxetine shares many of the common adverse effects of SSRIs, including (with the corresponding rates seen in people treated with placebo in parentheses): nausea 26% (9%), diarrhea 12% (8%), constipation 14% (9%), dry mouth 18% (12%), somnolence 23% (9%), insomnia 13% (6%), headache 18% (17%), hypomania 1% (0.3%), blurred vision 4%(1%), loss of appetite 6% (2%), nervousness 5% (3%), paraesthesia 4% (2%), dizziness 13% (6%), asthenia (weakness; 15% (6%)), tremor 8% (2%), sweating 11% (2%) and sexual dysfunction (≥10% incidence).[4] Most of these adverse effects are transient and go away with continued treatment. Central and peripheral 5-HT3 receptor stimulation is believed to result in the gastrointestinal effects observed with SSRI treatment.[31] Compared to other SSRIs it has a lower incidence of diarrhoea, a higher incidence of anticholinergic effects (e.g. dry mouth, constipation, blurred vision, etc.), sedation/somnolence/drowsiness, sexual side effects and weight gain.[32]
Due to reports of adverse withdrawal reactions upon terminating treatment, the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency recommends to reduce gradually over several weeks or months if the decision to withdraw is made.[33] See also Discontinuation syndrome (withdrawal).
Mania or hypomania may occur in 1% of patients with depression and up to 12% of patients with bipolar disorder.[34] This side effect can occur in individuals with no history of mania but it may be more likely to occur in those with bipolar or with a family history of mania.[35]
Suicide
Like other antidepressants, paroxetine may increase the risk of suicidal thinking and behaviour in children and adolescents.[36][37] The FDA conducted a statistical analysis of paroxetine clinical trials in children and adolescents in 2004, finding an increase in "suicidality" and ideation as compared to placebo; the trend for increased "suicidality" was observed in both trials for depression and for anxiety disorders.[38] In 2015 a paper published in the BMJ that reanalysed the original case notes, argued that in Study 329,[39] assessing paroxetine and imipramine against placebo in adolescents with depression, the incidence of suicidal behavior had been under-reported and efficacy exaggerated for paroxetine.[40]
Pregnancy
The American College of Obstetricians and Gynecologists recommends that for pregnant women and women planning to become pregnant, "treatment with all SSRIs or selective norepinephrine reuptake inhibitors or both during pregnancy be individualized and paroxetine use among pregnant women or women planning to become pregnant be avoided, if possible."[10] According to the prescribing information[41] "epidemiological studies have shown that infants born to women who had first trimester paroxetine exposure had an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects (VSDs and ASDs). In general, septal defects range from those that are symptomatic and may require surgery to those that are asymptomatic and may resolve spontaneously. If a patient becomes pregnant while taking paroxetine, she should be advised of the potential harm to the fetus. Unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant." These conclusions are supported by multiple systematic reviews and meta-analyses that found that, on average, the use of paroxetine during pregnancy is associated with about 1.5–1.7-fold increase in congenital birth defects, in particular, heart defects.[42][43][44][45][46]
Discontinuation syndrome
See also: SSRI discontinuation syndrome
Many psychoactive medications can cause withdrawal symptoms upon discontinuation from administration. Evidence has shown that paroxetine has among the highest incidence rates and severity of withdrawal syndrome of any medication of its class.[47][medical citation needed] Common withdrawal symptoms for paroxetine include nausea, dizziness, lightheadedness and vertigo; insomnia, nightmares and vivid dreams; feelings of electricity in the body, as well as crying and anxiety.[medical citation needed] Liquid formulation of paroxetine is available and allows a very gradual decrease of the dose, which may prevent discontinuation syndrome. Another recommendation is to temporarily switch to fluoxetine, which has a longer half-life and thus decreases the severity of discontinuation syndrome.[8][48][49]
Overdose
Acute overdosage is often manifested by emesis, lethargy, ataxia, tachycardia and seizures. Plasma, serum or blood concentrations of paroxetine may be measured to monitor therapeutic administration, confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities. Plasma paroxetine concentrations are generally in a range of 40–400 μg/L in persons receiving daily therapeutic doses and 200–2000 μg/L in poisoned patients. Postmortem blood levels have ranged from 1–4 mg/L in acute lethal overdose situations.[50][51] It is usually considered, along with the other SSRIs, sertraline and fluoxetine to be a low-risk drug in cases of overdose.[52]
Interactions
Interactions with other drugs acting on the serotonin system or impairing the metabolism of serotonin may increase the risk of Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reaction. Such reactions have been observed with SNRIs and SSRIs alone, but particularly with concurrent use of triptans, MAO inhibitors, antipsychotics or other dopamine antagonists.
The prescribing information states that paroxetine should "not be used in combination with an MAOI (including linezolid, an antibiotic which is a reversible non-selective MAOI), or within 14 days of discontinuing treatment with an MAOI", and should not be used in combination with pimozide, thioridazine, tryptophan, or warfarin.[41]
Paroxetine interacts with the following cytochrome P450 enzymes:[32]
- CYP2D6 for which it is both a substrate and a potent inhibitor.[1][32]
- CYP2B6 (strong) inhibitor.
- CYP3A4 (weak) inhibitor.
- CYP1A2 (weak) inhibitor.
- CYP2C9 (weak) inhibitor.
- CYP2C19 (weak) inhibitor.
Pharmacology
Paroxetine is the most potent and one of the most specific selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs).[53] It also binds to the allosteric site of the serotonin transporter, similarly, but less potently than escitalopram.[54] This activity of the drug on brain neurons is thought to be responsible for its antidepressant effects. Paroxetine inhibits the reuptake of norepinephrine more than the other SSRIs, just as sertraline inhibits the reuptake of dopamine more than the other SSRIs.[32]
Its affinities are as follows:[55][31]
- SERT (Ki = 0.08 nM)
- NET (Ki = 56.7 nM)
- DAT (Ki = 573.7 nM)
- The following muscarinic acetylcholine receptors (mAChRs):
- M1 (Ki=186 nM)
- M2 (Ki=340 nM)
- M3 (Ki=80 nM)
- M4 (Ki=320 nM)
- M5 (Ki=650 nM)
- α1 adrenoceptor (Ki>100,000 nM)
- Histamine H1 receptor (Ki=22,000 nM)
Society and culture
GlaxoSmithKline has paid substantial fines, paid settlements in class action lawsuits, and become the subject of several highly critical books in relation to its marketing of paroxetine, in particular the off-label marketing of paroxetine for children, the suppression of negative research results relating to its use in children, and allegations that it failed to warn consumers of substantial withdrawal effects associated with use of the drug.[15][16][17]
Withdrawal symptoms
In 2002 the U.S. FDA published a warning regarding "severe" discontinuation symptoms among those terminating paroxetine treatment, including paraesthesia, bad dreams, and dizziness. The Agency also warned of case reports describing agitation, sweating, and nausea. In connection with a Glaxo spokesperson's statement that withdrawal reactions occur only in 0.2% of patients and are "mild and short-lived", the International Federation of Pharmaceutical Manufacturers Associations said GSK had breached two of the Federation's codes of practice.[9]
Paroxetine prescribing information posted at GlaxoSmithKline now acknowledges the occurrence of a discontinuation syndrome, including serious discontinuation symptoms.[41]
Off-label marketing for children
See also: Study 329
In early 2004, GSK agreed to settle charges of consumer fraud for $2.5 million.[56] The legal discovery process also uncovered evidence of deliberate, systematic suppression of unfavorable Paxil research results. One of GSK's internal documents had said, "It would be commercially unacceptable to include a statement that efficacy [in children] had not been demonstrated, as this would undermine the profile of paroxetine".[57]
In 2012 the U.S. Justice Department announced that GSK had agreed to plead guilty and pay a $3 billion fine, in part for promoting the use of Paxil for children.[58]
Sales
In 2007, paroxetine was ranked 94th on the list of bestselling drugs, with over $1 billion in sales. In 2006, paroxetine was the fifth-most prescribed antidepressant in the United States retail market, with more than 19.7 million prescriptions.[59] In 2007, sales had dropped slightly to 18.1 million but paroxetine remained the fifth-most prescribed antidepressant in the U.S.[60][61]
Trade names
Aropax, Brisdelle, Deroxat, Paxil,[62] Pexeva, Paxtine, Paxetin, Paroxat, Paraxyl,[63] Sereupin and Seroxat.
Research
Several studies have suggested that paroxetine can be used in the treatment of premature ejaculation. In particular, intravaginal ejaculation latency time (IELT) was found to increase with 6–13-fold, which was somewhat longer than the delay achieved by the treatment with other SSRIs (fluvoxamine, fluoxetine, sertraline, and citalopram).[64][65][66] However, paroxetine taken acutely ("on demand") 3–10 hours before coitus resulted only in a "clinically irrelevant and sexually unsatisfactory" 1.5-fold delay of ejaculation and was inferior to clomipramine, which induced a fourfold delay.[66]
There is also evidence that paroxetine may be effective in the treatment of compulsive gambling[67] and hot flashes.[68]
Benefits of paroxetine prescription for diabetic neuropathy[69] or chronic tension headache[70] are uncertain.
Although the evidence is conflicting, paroxetine may be effective for the treatment of dysthymia, a chronic disorder involving depressive symptoms for most days of the year.[71]
Notes
- ^ United States Department of Justice, July 2012: "The United States alleges that, among other things, GSK participated in preparing, publishing and distributing a misleading medical journal article that misreported that a clinical trial of Paxil demonstrated efficacy in the treatment of depression in patients under age 18, when the study failed to demonstrate efficacy."[15][16][17]
References
- ^ a b c d e f "PRODUCT INFORMATION PAROXETINE SANDOZ 20mg FILM-COATED TABLETS" (PDF). TGA eBusiness Services. Sandoz Pty Ltd. 18 January 2012. Retrieved 22 November 2013.
- ^ a b c d e "PAROXETINE (paroxetine hydrochloride hemihydrate) tablet, film coated [Mylan Institutional Inc.]". DailyMed. Mylan Institutional Inc. January 2012. Retrieved 22 November 2013.
- ^ a b c d e "Paroxetine 20 mg Tablets – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Sandoz Limited. 21 March 2013. Retrieved 22 November 2013.
- ^ a b "Paxil, Paxil CR (paroxetine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 22 November 2013.
- ^ Katzman MA (2009). "Current considerations in the treatment of generalized anxiety disorder". CNS Drugs 23 (2): 103–20. doi:10.2165/00023210-200923020-00002. PMID 19173371.
- ^ Food and Drug Administration (June 28, 2013). "FDA NEWS RELEASE: FDA approves the first non-hormonal treatment for hot flashes associated with menopause".
- ^ Papakostas GI (2008). "Tolerability of modern antidepressants". J Clin Psychiatry 69 (Suppl E1): 8–13. PMID 18494538.
- ^ a b Haddad PM (2001). "Antidepressant discontinuation syndromes". Drug Saf 24 (3): 183–97. doi:10.2165/00002018-200124030-00003. PMID 11347722.
- ^ a b Tonks A (February 2002). "Withdrawal from paroxetine can be severe, warns FDA". BMJ 324 (7332): 260. doi:10.1136/bmj.324.7332.260. PMC 1122195. PMID 11823353.
- ^ a b "ACOG Committee Opinion No. 354: Treatment with selective serotonin reuptake inhibitors during pregnancy". Obstet Gynecol 108 (6): 1601–3. 2006. doi:10.1097/00006250-200612000-00058. PMID 17138801.
- ^ Yonkers, KA; Blackwell, KA; Glover, J; Forray, A (2014). "Antidepressant use in pregnant and postpartum women.". Annual review of clinical psychology 10: 369–92. doi:10.1146/annurev-clinpsy-032813-153626. PMID 24313569.
|access-date=requires|url=(help) - ^ Grigoriadis, S; VonderPorten, EH; Mamisashvili, L; Roerecke, M; Rehm, J; Dennis, CL; Koren, G; Steiner, M; Mousmanis, P; Cheung, A; Ross, LE (April 2013). "Antidepressant exposure during pregnancy and congenital malformations: is there an association? A systematic review and meta-analysis of the best evidence.". The Journal of clinical psychiatry 74 (4): e293–308. doi:10.4088/JCP.12r07966. PMID 23656855.
- ^ McGoey, Linsey; Jackson, Emily. "Seroxat and the suppression of clinical trial data: regulatory failure and the uses of legal ambiguity", Journal of Medical Ethics, 35(2), February 2009, pp. 107–112. doi:10.1136/jme.2008.025361 PMID 19181884
Le Noury, Joanna, et al. "Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence", BMJ, 351, 16 September 2015. doi:10.1136/bmj.h4320 PMID 26376805
- ^ Smith, Aaron (May 11, 2005). "New profit twist for drugmakers". CNN Money.
- ^ a b "GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data", United States Department of Justice, 2 July 2012.
- ^ a b United States v. GlaxoSmithKline, United States District Court for the District of Massachusetts, 26 October 2011 (for paroxetine, pp. 3–19).
- ^ a b Thomas, Katie; Schmidt, Michael S. "Glaxo Agrees to Pay $3 Billion in Fraud Settlement", The New York Times, 2 July 2012.
- ^ Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Scott J, Wittchen HU (2005). "Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology". Journal of Psychopharmacology 19 (6): 567–596. doi:10.1177/0269881105059253. PMID 16272179.
- ^ Baldwin D, Bobes J, Stein DJ, Scharwächter I, Faure M (1999). "Paroxetine in social phobia/social anxiety disorder. Randomised, double-blind, placebo-controlled study. Paroxetine Study Group". The British Journal of Psychiatry 175 (2): 120–6. doi:10.1192/bjp.175.2.120. PMID 10627793.
- ^ Yonkers KA, Gullion C, Williams A, Novak K, Rush AJ (1996). "Paroxetine as a treatment for premenstrual dysphoric disorder". Journal of Clinical Psychopharmacology. 16 (1): 3–8. doi:10.1097/00004714-199602000-00002. PMID 8834412.
- ^ Turner, Francis Joseph (2005). Social Work Diagnosis in Contemporary Practice. Oxford University Press US. ISBN 0-19-516878-X.
- ^ Hansen R, Gaynes B, Thieda P, et al. (October 2008). "Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants". Psychiatr Serv 59 (10): 1121–30. doi:10.1176/appi.ps.59.10.1121. PMC 2840386. PMID 18832497.
- ^ Dunner DL, Lipschitz A, Pitts CD, Davies JT (December 2005). "Efficacy and tolerability of controlled-release paroxetine in the treatment of severe depression: post hoc analysis of pooled data from a subset of subjects in four double-blind clinical trials". Clin Ther 27 (12): 1901–11. doi:10.1016/j.clinthera.2005.12.013. PMID 16507376.
- ^ Carpenter DJ, Fong R, Kraus JE, Davies JT, Moore C, Thase ME (November 2011). "Meta-analysis of efficacy and treatment-emergent suicidality in adults by psychiatric indication and age subgroup following initiation of paroxetine therapy: a complete set of randomized placebo-controlled trials". J Clin Psychiatry 72 (11): 1503–14. doi:10.4088/JCP.08m04927blu. PMID 21367354.
- ^ Barbui C, Furukawa TA, Cipriani A (Jan 29, 2008). "Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials". CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 178 (3): 296–305. doi:10.1503/cmaj.070693. PMC 2211353. PMID 18227449.
- ^ Tignol J, Stoker MJ, Dunbar GC (November 1992). "Paroxetine in the treatment of melancholia and severe depression". Int Clin Psychopharmacol 7 (2): 91–4. doi:10.1097/00004850-199207020-00005. PMID 1487627.
- ^ Gartlehner G, Gaynes BN, Hansen RA, et al. (November 2008). "Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians". Ann. Intern. Med. 149 (10): 734–50. doi:10.7326/0003-4819-149-10-200811180-00008. PMID 19017592.
- ^ Cipriani A, Furukawa TA, Salanti G, et al. (February 2009). "Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis". Lancet 373 (9665): 746–58. doi:10.1016/S0140-6736(09)60046-5. PMID 19185342.
- ^ FDA NEWS RELEASE: FDA approves the first non-hormonal treatment for hot flashes associated with menopause, Jun. 28, 2013http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm359030.htm
- ^ Orleans, Ronald J.; Li, Li; Kim, Myong-Jin; Guo, Jia; Sobhan, Mahboob; Soule, Lisa; Joffe, Hylton V. (2014). "FDA Approval of Paroxetine for Menopausal Hot Flushes". New England Journal of Medicine 370 (19): 1777–1779. doi:10.1056/NEJMp1402080. ISSN 0028-4793. PMID 24806158.
- ^ a b Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.
- ^ a b c d Ciraulo, DA; Shader, RI, ed. (2011). Pharmacotherapy of Depression. SpringerLink (2nd ed.) (New York, NY: Humana Press). doi:10.1007/978-1-60327-435-7. ISBN 978-1-60327-434-0.
- ^ "Press release, CHMP meeting on Paroxetine and other SSRIs" (PDF). European Medicines Agency. 2004-12-09. Retrieved 2007-08-24.
- ^ "www.accessdata.fda.gov" (PDF).
- ^ Morishita S, Arita S (October 2003). "Induction of mania in depression by paroxetine". Hum Psychopharmacol 18 (7): 565–8. doi:10.1002/hup.531. PMID 14533140.
- ^ "www.fda.gov" (PDF).
- ^ "FDA Launches a Multi-Pronged Strategy to Strengthen Safeguards for Children Treated With Antidepressant Medications".
- ^ Hammad TA (2004-08-16). "Review and evaluation of clinical data: relationship between psychotropic drugs and pediatric suicidality" (PDF). Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and Pediatric Advisory Committee. September 13–14, 2004. Briefing Information. FDA. p. 30. Retrieved 2009-01-27.
- ^ Keller MB; et al. (2001). "Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A Randomized, Controlled Trial". J Am Acad Child Adolesc Psychiatry 40 (7): 762–772. doi:10.1097/00004583-200107000-00010. PMID 11437014. CS1 maint: Explicit use of et al. (link)
- ^ Le Noury, Joanna, et al. "Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence", BMJ, 351, 16 September 2015. doi:10.1136/bmj.h4320 PMID 26376805
Godlee, Fiona. "Study 329", BMJ, 351, 17 September 2015. doi:10.1136/bmj.h4973
Doshi, Peter. "No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions about institutional responsibility", BMJ, 351, 16 September 2015. doi:10.1136/bmj.h4629 PMID 26377109
Henry, David; Fitzpatrick, Tiffany. "Liberating the data from clinical trials", BMJ, 351, 16 September 2015. doi:10.1136/bmj.h4601 PMID 26377210
Boseley, Sarah. "Seroxat study under-reported harmful effects on young people, say scientists", The Guardian, 16 September 2015.
- ^ a b c "PAXIL (paroxetine hydrochloride) Tablets and Oral Suspension: PRESCRIBING INFORMATION". Research Triangle Park, NC: GlaxoSmithKline. August 2007. Archived from the original (PDF) on 2011-08-25. Retrieved 2007-08-14.
- ^ Thormahlen GM (October 2006). "Paroxetine use during pregnancy: is it safe?". Ann Pharmacother 40 (10): 1834–7. doi:10.1345/aph.1H116. PMID 16926304.
- ^ Way CM (2007). "Safety of newer antidepressants in pregnancy". Pharmacotherapy 27 (4): 546–52. doi:10.1592/phco.27.4.546. PMID 17381382.
- ^ Bellantuono C, Migliarese G, Gentile S (2007). "Serotonin reuptake inhibitors in pregnancy and the risk of major malformations: a systematic review". Hum Psychopharmacol 22 (3): 121–8. doi:10.1002/hup.836. PMID 17397101.
- ^ Källén B (July 2007). "The safety of antidepressant drugs during pregnancy". Expert Opin Drug Saf 6 (4): 357–70. doi:10.1517/14740338.6.4.357. PMID 17688379.
- ^ Bar-Oz B, Einarson T, Einarson A, Boskovic R, O'Brien L, Malm H, Bérard A, Koren G (May 2007). "Paroxetine and congenital malformations: meta-Analysis and consideration of potential confounding factors". Clin Ther 29 (5): 918–26. doi:10.1016/j.clinthera.2007.05.003. PMID 17697910.
- ^ "Anti-depressant addiction warning". BBC News. 2001-06-11. Retrieved 2010-05-21.
- ^ Haddad PM, Anderson IM (November 2007). "Recognising and managing antidepressant discontinuation symptoms". Advances in Psychiatric Treatment 13 (6): 447–457. doi:10.1192/apt.bp.105.001966.
- ^ on Antidepressants & Halting SSRIs by Dr David Healy MD, FRCPsych[dead link]. benzo.org.uk. Retrieved on 2013-04-23.
- ^ Goeringer KE, Raymon L, Christian GD, Logan BK (May 2000). "Postmortem forensic toxicology of selective serotonin reuptake inhibitors: a review of pharmacology and report of 168 cases". J. Forensic Sci. 45 (3): 633–48. PMID 10855970.
- ^ R. Baselt,Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1190–1193.
- ^ White N, Litovitz T, Clancy C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type". Journal of Medical Toxicology 4 (4): 238–250. doi:10.1007/BF03161207. PMC 3550116. PMID 19031375.
- ^ Mellerup ET, Plenge P (July 1986). "High affinity binding of3H-paroxetine and3H-imipramine to rat neuronal membranes". Psychopharmacology 89 (4): 436–9. doi:10.1007/BF02412117. PMID 2944152.
- ^ Mansari ME, Wiborg O, Mnie-Filali O, Benturquia N, Sánchez C, Haddjeri N (February 2007). "Allosteric modulation of the effect of escitalopram, paroxetine and fluoxetine: in-vitro and in-vivo studies". The International Journal of Neuropsychopharmacology 10 (1): 31–40. doi:10.1017/S1461145705006462. PMID 16448580.
- ^ Roth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 22 November 2013.
- ^ Angell M (15 January 2009). "Drug Companies & Doctors: A Story of Corruption". New York Review of Books 56 (1).
- ^ Kondro W, Sibbald B (March 2004). "Drug company experts advised staff to withhold data about SSRI use in children". CMAJ 170 (5): 783. doi:10.1503/cmaj.1040213. PMC 343848. PMID 14993169.
- ^ Thomas, Katie; Schmidt, Michael S. (July 2, 2012). "Glaxo Agrees to Pay $3 Billion in Fraud Settlement". The New York Times.
- ^ The paroxetine prescriptions were calculated as a total of prescriptions for Paxil CR and generic paroxetine using data from the charts for generic and brand-name drugs."Top 200 generic drugs by units in 2006. Top 200 brand-name drugs by units". Drug Topics, Mar 5, 2007. Retrieved 2007-04-08.
- ^ The paroxetine prescriptions were calculated as a total of prescriptions for Paxil CR and generic paroxetine using data from the charts for generic and brand-name drugs."Top 200 generic drugs by units in 2007". Drug Topics. February 18, 2008. Archived from the original on 2009-07-18. Retrieved 2008-10-23.
- ^ "Top 200 brand drugs by units in 2007". Drug Topics, Feb 18, 2008. Archived from the original on 2009-06-29. Retrieved 2008-10-23.
- ^ Coleman, Andrew (2006). Dictionary of Psychology (Second Edition). Oxford University Press. p. 552.
- ^ Coleman, Andrew (2006). Dictionary of Psychology (Second Edition). Oxford University Press. p. 161.
- ^ Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B (August 1998). "Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline". Journal of Clinical Psychopharmacology 18 (4): 274–81. doi:10.1097/00004714-199808000-00004. PMID 9690692.
- ^ Waldinger MD, Zwinderman AH, Olivier B (2001). "SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram". Journal of Clinical Psychopharmacology 21 (6): 556–60. doi:10.1097/00004714-200112000-00003. PMID 11763001.
- ^ a b Waldinger MD, Zwinderman AH, Olivier B (2004). "On-demand treatment of premature ejaculation with clomipramine and paroxetine: a randomized, double-blind fixed-dose study with stopwatch assessment". Eur. Urol. 46 (4): 510–5; discussion 516. doi:10.1016/j.eururo.2004.05.005. PMID 15363569.
- ^ Kim SW, Grant JE, Adson DE, Shin YC, Zaninelli R (2002). "A double-blind placebo-controlled study of the efficacy and safety of paroxetine in the treatment of pathological gambling". Journal of Clinical Psychiatry 63 (6): 501–7. doi:10.4088/JCP.v63n0606. PMID 12088161.
- ^ Weitzner MA, Moncello J, Jacobsen PB, Minton S (2002). "A pilot trial of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer". Journal of Pain and Symptom Management 23 (4): 337–345. doi:10.1016/S0885-3924(02)00379-2. PMID 11997203.
- ^ Sindrup SH, Gram LF, Brøsen K, Eshøj O, Mogensen EF (1999). "The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms". Pain 42 (2): 135–144. doi:10.1016/0304-3959(90)91157-E. PMID 2147235.
- ^ Langemark M, Olesen J (1994). "Sulpiride and paroxetine in the treatment of chronic tension-type headache. An explanatory double-blind trial". Headache 34 (1): 20–4. doi:10.1111/j.1526-4610.1994.hed3401020.x. PMID 8132436.
- ^ Gartlehner G, Gaynes BN, Hansen RA, Thieda P, DeVeaugh-Geiss A, Krebs EE, Moore CG, Morgan L, Lohr KN (November 2008). "Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians". Ann. Intern. Med. 149 (10): 734–50. doi:10.7326/0003-4819-149-10-200811180-00008. PMID 19017592.
External links
| Wikimedia Commons has media related to Paroxetine. |
- List of international brand names for paroxetine
- Detailed Paroxetine Consumer Information: Uses, Precautions, Side Effects from medlibrary.org
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
- 1. 成人における双極性障害：抗うつ剤による大うつ病の治療 bipolar disorder in adults treating major depression with antidepressants
- 2. 成人における単一恐怖に対する薬物療法 pharmacotherapy for specific phobia in adults
- 3. 成人における初期治療に不応の線維筋痛症の治療 treatment of fibromyalgia in adults not responsive to initial therapies
- 4. 成人における単極性うつ病および選択的セロトニン再取り込み阻害剤（SSRIs）：
薬理学、投与方法、および副作用 unipolar depression in adults and selective serotonin reuptake inhibitors ssris pharmacology administration and side effects - 5. 妊娠女性におけるうつ病：管理 depression in pregnant women management
English Journal
- Involvement of organic cation transporter 2 inhibition in potential mechanisms of antidepressant action.
- Wang K1, Sun S1, Li L1, Tu M1, Jiang H2.
- Progress in neuro-psychopharmacology & biological psychiatry.Prog Neuropsychopharmacol Biol Psychiatry.2014 Aug 4;53:90-8. doi: 10.1016/j.pnpbp.2014.03.005. Epub 2014 Mar 20.
- Novel antidepressants or treatment strategies that may offer a more rapid onset of action, improved efficacy, and greater tolerability are in desperate need. Because current clinically utilized antidepressants, which target high-affinity transporters for serotonin and norepinephrine, fail to provide
- PMID 24657329
- Acute toxicity of 8 antidepressants: What are their modes of action?
- Minguez L1, Farcy E2, Ballandonne C3, Lepailleur A3, Serpentini A4, Lebel JM4, Bureau R3, Halm-Lemeille MP3.
- Chemosphere.Chemosphere.2014 Aug;108:314-9. doi: 10.1016/j.chemosphere.2014.01.057. Epub 2014 Feb 14.
- Currently, the hazard posed by pharmaceutical residues is a major concern of ecotoxicology. Most of the antidepressants belong to a family named the Cationic Amphipathic Drugs known to have specific interactions with cell membranes. The present study assessed the impact of eight antidepressants belo
- PMID 24534154
- An investigation of Temperament and Character Inventory items for predicting the response to paroxetine treatment in patients with major depressive disorder.
- Tomita T1, Ishioka M1, Kaneda A1, Sugawara N1, Nakagami T1, Nakamura K1, Yasui-Furukori N2.
- Journal of affective disorders.J Affect Disord.2014 Aug;165:109-13. doi: 10.1016/j.jad.2014.04.076. Epub 2014 May 4.
- BACKGROUND: Previous studies have reported associations between Temperament and Character Inventory (TCI) dimension scores and the response to treatment in patients with major depressive disorder (MDD). We aimed to determine which TCI items could predict the response to treatment with paroxetine in
- PMID 24882186
Japanese Journal
- 帯状疱疹の疼痛に対するパロキセチンの治療効果
- 宿輪 哲生,石川 博士
- 日本皮膚科学会雑誌 121(8), 1601-1606, 2011-08
- NAID 40018897472
- 男性更年期外来におけるSSRI長期投与の実際
- 石蔵 文信
- 心身医学 51(7), 644-649, 2011-07-01
- … 男性更年期外来を受診する患者は,気分障害や不安障害を伴うことが多い.そこで,当院の男性更年期外来を受診し,paroxetine(SSRI)を長期投与した患者108例の経過について,1年以内に治療が終了した症例(短期終了群),1年以上治療後に終了した症例(長期終了群),現在も治療中である症例(継続群)に分けて検討した.各群の患者背景については,Self-rating Depression Scale(SDS)スコアが長期終了群で他の群より有意に低かったが,年齢,特性不 …
- NAID 110008673141
Related Links
- 中込 私も大学病院ですが、私の施設では単剤治療を重視していますから、 Paroxetine の用量については十分量である30mg以上、は使おうということで、20mgでしばらく待つ ということはあまりない。ただうつ病の場合、効果があ ...
- Summary The metabolism of paroxetine is accomplished in part by cytochrome CYP2D6. Coadministration of paroxetine with other drugs that are metabolized by this isozyme should be approached with caution. Due to the risk of ...
- Paroxetine is a prescription medication used to treat depression, panic disorder, hot flashes related to menopause, and... ... Tell your doctor about all the medicines you take including prescription and non-prescription medicines ...
Related Pictures
★リンクテーブル★
| リンク元 | 「抗うつ薬」「パロキセチン」「選択的セロトニン再取り込み阻害薬」「PAX」 |
| 拡張検索 | 「paroxetine hydrochloride hydrate」 |
「抗うつ薬」
- 英
- antidepressant, antidepressants
- 関
- 薬理学、そううつ病、精神疾患
作用機序
三環系抗うつ薬 tricyclic antidepressant
- ２つの説がある。
- 1. (急性作用)シナプス前膜におけるノルアドレナリン、セロトニンの再取り込み↓→シナプス間隙における薬剤濃度↑
- 2. (慢性作用)(2週間後)シナプス後膜における受容体の数↓
- 慢性作用はシナプス間隙のノルアドレナリン、セロトニン濃度が上昇した結果、シナプス後膜の受容体が減少したために出現すると考えられる。
抗うつ薬
- 三環系
- 四環系
- 非定型抗うつ薬 atypical agent
副作用
- Adams and s Principles of Neurology, Ninth Edition Allan Ropper p.1474
| 不眠、焦燥 | 鎮静 | 低血圧 | 抗コリン作用 | 消化管症状(嘔吐等) | 性機能低下 | 体重増加 | ||
| 三環系 | アミトリプチリン | ± | 2+ | 2+ | 3+ | ± | ＋ | 2+ |
| 三環系 | ドスレピン | ± | 2+ | 2+ | 2+ | ± | ＋ | 2+ |
| 三環系 | イミプラミン | 2+ | ＋ | 2+ | 2+ | ± | ＋ | 2+ |
| SSRI | フルオキセチン | 2+ | ± | ± | ＋ | 2+ | 2+ | ＋ |
| SSRI | パロキセチン | 2+ | ± | ± | ± | 2+ | 2+ | ＋ |
| SSRI | セルトラリン | 2+ | ± | ± | ± | 2+ | 2+ | ＋ |
| SSRI | フルボキサミン | 2+ | ＋ | ± | ± | 2+ | 2+ | ＋ |
| SSRI | シタロプラム | 2+ | ± | ± | ± | 2+ | 2+ | ＋ |
| SSRI | エスシタロプラム | 2+ | ± | ± | ± | 2+ | 2+ | ＋ |
| SNRI | デシプラミン | ＋ | ± | 2+ | ＋ | ± | ＋ | ＋ |
| SNRI | ノルトリプチリン | ＋ | ＋ | ＋ | ＋ | ± | ＋ | ＋ |
| SNRI | マプロチリン | ＋ | ± | ＋ | ＋ | ± | ＋ | 2+ |
| SNRI | ベンラファキシン | 2+ | ± | ± | ± | 2+ | 2+ | ± |
| SNRI | デュロキセチン | ± | ＋ | ± | ＋ | ＋ | ± | ± |
| NDRI | ブプロピオン | 2+ | ± | ± | ＋ | ＋ | ± | ± |
| MAOI | フェネルジン | 2+ | ＋ | 2+ | ＋ | ＋ | 2+ | ＋ |
| MAOI | トラニルシプロミン | 2+ | ＋ | 2+ | ＋ | ＋ | 2+ | ＋ |
| MAOI | イソカルボキサジド | 2+ | ± | 2+ | ＋ | ＋ | 2+ | 2+ |
| MAOI | セレギリン | ＋ | ± | ＋ | ＋ | ＋ | ＋ | ＋ |
| NaSSA | ミルタザピン | ± | 3+ | ＋ | ± | ± | ± | 3+ |
| 非定型 | ネファゾドン | ± | 2+ | ＋ | ＋ | ＋ | ± | ＋ |
| 非定型 | トラゾドン | ± | 3+ | ＋ | ± | ＋ | 2+ | ＋ |
「パロキセチン」
分類
適応
- うつ病・うつ状態、パニック障害、強迫性障害、社会不安障害
禁忌
- 1. 本剤の成分に対し過敏症の既往歴のある患者
- 2. MAO阻害剤を投与中あるいは投与中止後２週間以内の患者(「相互作用」及び「重大な副作用」の項参照)
- 3. チオリダジンを投与中の患者
- 4. ピモジドを投与中の患者
副作用
- うつ病・うつ状態患者、パニック障害患者、強迫性障害患者及び社会不安障害患者を対象とした本邦での臨床試験において、総症例1424例中975例（68.5％）に臨床検査値異常を含む副作用が報告された。その主なものは、傾眠336例（23.6％）、嘔気268例（18.8％）、めまい186例（13.1％）、頭痛132例（9.3％）、便秘113例（7.9％）であった（承認時）。
- うつ病・うつ状態患者、パニック障害患者を対象とした使用成績調査及び強迫性障害患者を対象とした特定使用成績調査において、3239例中503例（15.5％）に臨床検査値異常を含む副作用が報告された。その主なものは、嘔気157例（4.8％）、傾眠120例（3.7％）、食欲不振42例（1.3％）、めまい42例（1.3％）であった（第13回安全性定期報告時）。
添付文書
http://www.info.pmda.go.jp/go/pack/1179041F1025_2_23/
「選択的セロトニン再取り込み阻害薬」
- フルオキセチン fluoxitine
- フルボキサミン fluvoxamine
- パロキセチン paroxetine
特徴
- TCAと違いcaridiotoxicityがない。また、ムスカリン受容体、ヒスタミン受容体、アドレナリン受容体、ドパミン受容体に結合しない。
適応
副作用
- some degree of sexual dysfunction
- GI distress
- sertraline：diarrhea
- paroxetine：comstipation
- serotonin syndrome: rare but dangeraous elevation of 5HT： can occur when both an SSRI and a monoamine oxidase inhibitor are administered simultaneously.
- hyperthermia, muscle rigidity, myoclonus, and rapid fluctuations in mental status and vital signs.
「PAX」
- パックス 発生に関わる転写因子
- パロキセチン paroxetine